Category: Journal Club

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Journal Club: Therapeutic Administration of 131-I for Differentiated Thyroid Cancer: Radiation Dose to Ovaries and Outcome of Pregnancies

The journal club has been getting neglected recently. Trying to remedy that for this year.
From this month’s JNM comes a paper on I-131 therapy and pregnancy, always a very hot issue. The paper is a follow-up to an earlier study from 1996 which said that I-131 exposure from thyroid therapy did not affect the outcome of subsequent pregnancies.

In the current paper, the number of patients with pregnancies within a year following 131I therapy was increased over the previous study (n=158 vs n=96) enabling better statistical analysis of the results.

One of the more interesting (I thought) results from the study was that the percentage of miscarriages following treatment for thyroid cancer (either surgical or radioiodine therapy) increased. However, the percentages were essentially the same whether the treatment was surgical or with radioiodine (20.7% vs 19%).

There are a lot of statistics and tables presented in the paper looking at a myriad of things. However, the bottom line is that the authors did not find any evidence to support a common precaution that female patients avoid becoming pregnant for one year following treatment for thyroid cancer.

Garsi J-P, Schlumberger M, Rubino C, et al. Therapeutic administration of 131I for differentiated thyroid cancer: radiation dose to ovaries and outcome of pregnancies. J Nucl Med. 2008;49:845-852

Abstract:

Radiation is known to be mutagenic. The present study updates a 10-y-old study regarding pregnancy outcome and the health of offspring of women previously exposed to radioiodine (131I) during thyroid carcinoma treatment, by doubling the number of pregnancies that occurred after exposure. Methods: Data on 2,673 pregnancies were obtained by interviewing female patients who were treated for thyroid carcinoma but had not received significant external radiation to the ovaries. Results: The incidence of miscarriages was 10% before any treatment for thyroid cancer; this percentage increased after surgery for thyroid cancer, both before (20%) and after (19%) 131I treatment, with no variation according to the cumulative dose. In contrast to previously reported data, miscarriages were not significantly more frequent in women treated with radioiodine during the year before conception, not even in women who had received more than 370 MBq during that year. The incidences of stillbirths, preterm births, low birth weight, congenital malformations, and death during the first year of life were not significantly different before and after 131I therapy. The incidences of thyroid and nonthyroid cancers were similar in children born either before or after the mother’s exposure to radioiodine. Conclusion: There is no evidence that exposure to radioiodine affects the outcomes of subsequent pregnancies and offspring. The question as to whether the incidences of malformations and thyroid and nonthyroid cancers are related to gonadal irradiation remains to be established. The doubling dose is still being heatedly debated, and the value of 1 Gy as the doubling dose in humans should be reevaluated.

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Journal Club: From Baking a Cake to Solving the Schrödinger Equation

This latest installment of the journal club isn’t exactly medical physics related, but it was something that I thought was interesting more from a topical point of view rather than the actual research itself.

The title of the paper, From Baking a Cake to Solving the Schrödinger Equation, may give the impression of being just another trivial waste of time and a candidate for an Ig Nobel award.

Look a little deeper and it actually turns out to be much more.

Physics is all about developing, describing and modeling systems or processes, which is exactly what this paper is about. Once you have a decent model, you use it to make predictions and design experiments to verify those predictions. The author takes a seemingly trivial process (how changes in cake dimension and volume affect baking time) and attempts to describe the process mathematically using well known equations and experimental results.

Found via Talk Like A Physicist

First comes the initial model. The authors begin with the diffusion equation.

Along with some known initial conditions, the equation can be solved to produce a solution that approximates the cake baking process. In the case of the paper, the solution provides the baking time given the dimensions of the cake.

Once the solutions have been obtained, it’s now possible to visualize the theoretical behaviour of the system. However, this still needs to be correlated to the actual observed behaviour, which is where the experimental part comes in. If the experimental results deviate from the expected theoretical results, it probably means that some of the assumptions in the model were incorrect and need to be modified. Usually it’s possible to figure out how the model needs to be modified by studying the differences between the theoretical and experimental results. With the modified model, a new set of solutions can be created and then verified against experimental results.

With enough iterations, the model becomes accurate enough to make predictions that can be verified experimentally. Often new experiments need to be designed in order to verify any predictions made. Sometimes current technology is insufficient and verifying predictions must wait years or decades before it can be done. If you’re really clever, you notice that the solutions of the model can be applied to other systems, or you notice that the solution or equations resemble a process in a completely unrelated field. In the paper, the author notes the similarity between the diffusion equation and Shrödinger’s equation and analyzes not only what the solutions mean when applied to the Shrödinger equation, but also the limitations of the solutions.

Thus, rather than being an apparently trivial paper, this paper is really a very impressive study of what physics and the process of doing physics is all about.

Abstract:

The primary emphasis of this study has been to explain how modifying a cake recipe by changing either the dimensions of the cake or the amount of cake batter alters the baking time. Restricting our consideration to the génoise, one of the basic cakes of classic French cuisine, we have obtained a semi-empirical formula for its baking time as a function of oven temperature, initial temperature of the cake batter, and dimensions of the unbaked cake. The formula, which is based on the Diffusion equation, has three adjustable parameters whose values are estimated from data obtained by baking génoises in cylindrical pans of various diameters. The resulting formula for the baking time exhibits the scaling behavior typical of diffusion processes, i.e. the baking time is proportional to the (characteristic length scale) of the cake. It also takes account of evaporation of moisture at the top surface of the cake, which appears to be a dominant factor affecting the baking time of a cake. In solving this problem we have obtained solutions of the Diffusion equation which are interpreted naturally and straightforwardly in the context of heat transfer; however, when interpreted in the context of the Schrödinger equation, they are somewhat peculiar. The solutions describe a system whose mass assumes different values in two different regions of space. Furthermore, the solutions exhibit characteristics similar to the evanescent modes associated with light waves propagating in a wave guide. When we consider the Schrödinger equation as a non-relativistic limit of the Klein-Gordon equation so that it includes a mass term, these are no longer solutions.

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Journal Club: Simultaneous Acquisition of Multislice PET and MR Images: Initial Results with a MR-Compatible PET Scanner

Today’s journal club article comes from JNM and talks about some new bleeding-edge tech alluded to in the previous journal club article: PET and MRI.

The technology presented in the paper is pretty bleeding edge and represents 2 years of instrumentation and development work. They present a prototype PET unit for use in a small animal MR magnet operating at 7T. Their solution to solving the problem of detecting light from the scintillator crystals was to use position sensitive photodiodes, which are less prone to distortions from magnetic field effects. In order to reduce electrical noise in the detectors, the authors used a cold nitrogen gas to cool the detectors. This is understandably a significant limitation for real world clinical work, but not insurmountable. Several interesting effects were noted with using the photodiodes and fiberoptic coupling and are nicely illustrated with sample images.

Some very interesting development work here that shows a lot of potential. It’s not the first PET/MRI hybrid unit developed or the only one being worked on, but the design and implementation the authors have come up with has the potential of retrofitting existing MR scanners with the capability rather than having to get a new magnet. Obviously it’s still several years away from any kind of implementation for human use, but in the meantime a working unit for small animal imaging would probably yield some very useful information for researchers.

Ciprian Catana, Yibao Wu, Martin S. Judenhofer, Jinyi Qi, Bernd J. Pichler and Simon R. Cherry, “Simultaneous Acquisition of Multislice PET and MR Images: Initial Results with a MR-Compatible PET Scanner“, J Nucl Med 47: 1968-1976

Abstract:

PET and MRI are powerful imaging techniques that are largely complementary in the information they provide. We have designed and built a MR-compatible PET scanner based on avalanche photodiode technology that allows simultaneous acquisition of PET and MR images in small animals.
Methods: The PET scanner insert uses magnetic field-insensitive, position-sensitive avalanche photodiode (PSAPD) detectors coupled, via short lengths of optical fibers, to arrays of lutetium oxyorthosilicate (LSO) scintillator crystals. The optical fibers are used to minimize electromagnetic interference between the radiofrequency and gradient coils and the PET detector system. The PET detector module components and the complete PET insert assembly are described. PET data were acquired with and without MR sequences running, and detector flood histograms were compared with the ones generated from the data acquired outside the magnet. A uniform MR phantom was also imaged to assess the effect of the PET detector on the MR data acquisition. Simultaneous PET and MRI studies of a mouse were performed ex vivo.
Results: PSAPDs can be successfully used to read out large numbers of scintillator crystals coupled through optical fibers with acceptable performance in terms of energy and timing resolution and crystal identification. The PSAPD-LSO detector performs well in the 7-T magnet, and no visible artifacts are detected in the MR images using standard pulse sequences.
Conclusion: The first images from the complete system have been successfully acquired and reconstructed, demonstrating that simultaneous PET and MRI studies are feasible and opening up interesting possibilities for dual-modality molecular imaging studies.

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Journal Club: The 2006 Henry N Wagner Lecture

Today’s journal club article isn’t really an actual research paper, but more of a ‘where are we now and where are we going’ type of article written by a prominent nuclear medicine physicist, Simon Cherry. It comes from the November issue of The Journal of Nuclear Medicine. The article is The 2006 Henry N. Wagner Lecture: Of Mice and Men (and Positrons)—Advances in PET Imaging Technology (J Nucl Med 2006 47: 1735-1745)

By far the most interesting part of Cherry’s article is where he looks forward to the future of PET imaging and raises the idea of PET/MRI imaging and whole-body PET/MRI imaging.. Rather than using conventional photomultiplier tubes, which would be rendered useless by the magnetic field from the MRI unit, the scintillation light would be detected by avalanche photodiodes. Very tantalizing possibilities indeed.

Abstract:

There have been major advances in PET technology that cumulatively have helped improve image quality, increased the range of applications for PET, and contributed to the more widespread use of PET. Examples of these technologic advances include whole-body imaging, 3-dimensional imaging, new scintillator materials, iterative reconstruction algorithms, combined PET/CT, and preclinical PET. New advances on the immediate horizon include the reintroduction of time-of-flight PET, which takes advantage of the favorable timing properties of newer scintillators; the integration of PET and MRI scanners into a dual-modality imaging system; and the possibility of further significant improvements in spatial resolution in preclinical PET systems. Sensitivity remains a limiting factor in many PET studies. Although, conceptually, huge gains in sensitivity are still possible, realizing these gains is thwarted largely by economic rather than scientific concerns. Predicting the future is fraught with difficulty; nonetheless, it is apparent that ample opportunities remain for new development and innovation in PET technology that will be driven by the demands of molecular medicine, notably sensitive and specific molecular diagnostic tools and the ability to quantitatively monitor therapeutic entities that include small molecules, peptides, antibodies, nanoparticles, DNA/RNA, and cells.

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Journal Club: Breast milk excretion of radiopharmaceuticals: mechanisms, findings, and radiation dosimetry

The latest installment of the journal club is an older article from JNM but still relevant and looks at the radiation dose to infants from isotopes excreted through breast milk. Breast milk excretion of radiopharmaceuticals: mechanisms, findings, and radiation dosimetry by Stabin and Breitz (J Nucl Med 41, 863-873 (2000)) is more of a review article and summarizes some of the past literature looking at concentrations of various radioisotopes and radiopharmaceuticals excreted in breast milk of female patients undergoing nuclear medicine procedures.

The article starts off with a short discussion on the basic anatomy and physiology of the breast and then goes into a nice concise compilation of breast milk concentrations and infant doses for 25 radiopharmaceuticals. The concentrations of radioactivity in breast milk turns out to be relatively low, but not insignificant except for a few of the usual isotopes, most notably I-131 and Ga-67. Suggested times for how long breast feeding should be stopped for are also given. Table 2 of the paper is probably most useful for anybody who needs to do some dosimetry calculations for physicians or concerned patients.

A good paper to add to the library for any medical or health physicist that finds themselves doing patient dosimetry.

Abstract:

The excretion of radiopharmaceuticals in breast milk is studied to understand excretion mechanisms and to determine recommended breast feeding interruption times for many compounds based on the radiation absorbed dose estimated. A literature review is summarized, providing information on breast milk excretion of many radiopharmaceuticals, including the observed fractions of administered activity excreted and the disappearance half-times. Radiation doses to the infant and to the mother’s breasts have been calculated using mathematical models of the activity clearance into milk, with interruption schedules for the nursing infant derived using a dose criteria of 1 mSv effective dose to the infant. In only 9 of the 25 radiopharmaceuticals considered here is interruption in breast feeding thought necessary. However, in the literature, breast milk concentrations of radiopharmaceuticals and half-times varied considerably between subjects, and individual measurements are encouraged to raise confidence in specific cases. The absorbed dose to the mother’s breast approaches 10-20 mGy (1-2 rad) for a few nuclides, but most doses are quite low. Therapeutic administration of 131I-NaI is a special case, for which the breast dose for a 5550 MBq (150 mCi) administration could approach 2 Gy (200 rad). In this article, these data are discussed, with the aim of assisting others in evaluating the significance of administration of radiopharmaceuticals to lactating women. An example of a sampling scheme and calculation to determine dose for a specific patient is also developed.